ADAM17 promotes epithelial-mesenchymal transition via TGF-β/Smad pathway in gastric carcinoma cells

Xu,Min; Zhou,Hailang; Zhang,Chunli; He,Junbo; Wei,Hong; Zhou,Meng; Lu,Ying; Sun,Yaocheng; Ding,Jerry Wanming; Zeng,Jian; Peng,Wanxin; Du,Fengyi; Gong,Aihua

doi:10.3892/ijo.2016.3744

ADAM17 promotes epithelial-mesenchymal transition via TGF-β/Smad pathway in gastric carcinoma cells

Authors:
- Min Xu
- Hailang Zhou
- Chunli Zhang
- Junbo He
- Hong Wei
- Meng Zhou
- Ying Lu
- Yaocheng Sun
- Jerry Wanming Ding
- Jian Zeng
- Wanxin Peng
- Fengyi Du
- Aihua Gong
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Affiliations: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China, Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, N6A 5C1, Canada, Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
Published online on: October 21, 2016 https://doi.org/10.3892/ijo.2016.3744
Pages: 2520-2528

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Abstract

Although a disintegrin and metalloproteinase-17 (ADAM17) overexpression has been demonstrated in numerous human tumors including gastric cancer, its role in gastric cancer development remains to be clarified. In the present study, we identify that ADAM17 activates TGF-β/Smad signaling to promote epithelial-mesenchymal transition (EMT) in gastric cancer cells. We found that ADAM17 promotes proliferation, migration and invasion in gastric carcinoma cells. Subsequently, we revealed that silencing ADAM17 induces the expression of epithelial marker of E-cadherin and downregulates expression of mesenchymal markers including N-cadherin, vimentin and Snail in MGC803 and MKN45 cells, whereas ADAM17 overexpression reverses these changes in BGC823 and HGC27 cells. Furthermore, ADAM17 knockdown significantly inhibits the expression of TGF-β and its downstream signaling molecules p-Smad2 and p-Smad3 in MGC803 and MKN45 cells. Consistently, ADAM17 overexpression reversed these changes in BGC823 and HGC27 cells. These results suggest that ADAM17 promotes epithelial-mesenchymal transition via the TGF-β/Smad pathway. Collectively, the present study demonstrates that ADAM17 plays a critical role in the development of gastric cancer and provides a potential therapeutic target for gastric cancer.

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